Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, China.
Metabolic Syndrome Research Center, The Second Xiangya Hospital, Central South University, Changsha, China.
Obesity (Silver Spring). 2020 Aug;28(8):1467-1476. doi: 10.1002/oby.22863. Epub 2020 Jun 23.
Recent studies have shown that microRNAs (miRNAs/miRs) play key roles in adipogenesis. This study aimed to investigate the role and underlying mechanism of miR-182 in adipogenesis.
This study used the 3T3-L1 cell line and human visceral adipose tissue (VAT)-derived adipocytes to determine the role of miR-182 in adipogenesis. Adipose tissues from mice with high-fat diet-induced obesity, ob/ob mice, or human individuals with obesity were used to determine the association of miR-182 levels with obesity. A luciferase reporter assay was used to determine the target of miR-182.
The expression level of miR-182 was greatly downregulated during white adipogenesis and markedly lower in the VAT of mice and humans with obesity. Ectopic expression of miR-182 in 3T3-L1 cells and human adipocytes suppressed the formation of lipid droplets and the expression of adipogenic genes. The luciferase reporter assay showed that miR-182 targeted the 3'-untranslated sequence of CCAAT/enhancer-binding protein α (C/EBPα) directly. In addition, glucocorticoids negatively regulated miR-182 expression, which, in turn, suppressed the glucocorticoid-induced expression of C/EBPα.
Taken together, our studies identified miR-182 as a novel negative regulator of adipogenesis and a potential therapeutic target for obesity.
最近的研究表明 microRNAs（miRNAs/miRs）在脂肪生成中发挥关键作用。本研究旨在探讨 miR-182 在脂肪生成中的作用及其潜在机制。
本研究使用 3T3-L1 细胞系和人内脏脂肪组织（VAT）来源的脂肪细胞来确定 miR-182 在脂肪生成中的作用。使用高脂肪饮食诱导肥胖的小鼠、ob/ob 小鼠或肥胖个体的脂肪组织来确定 miR-182 水平与肥胖的相关性。使用荧光素酶报告基因检测来确定 miR-182 的靶标。
miR-182 的表达水平在白色脂肪生成过程中显著下调，在肥胖小鼠和人类的 VAT 中明显降低。在 3T3-L1 细胞和人脂肪细胞中异位表达 miR-182 抑制了脂滴的形成和脂肪生成基因的表达。荧光素酶报告基因检测表明，miR-182 直接靶向 CCAAT/增强子结合蛋白α（C/EBPα）的 3'非翻译区。此外，糖皮质激素负调控 miR-182 的表达，进而抑制糖皮质激素诱导的 C/EBPα 表达。
综上所述，我们的研究确定了 miR-182 是脂肪生成的一种新型负调控因子，也是肥胖的潜在治疗靶点。
